Sequential activation RF electrode set for renal nerve ablation

ABSTRACT

A catheter includes a flexible shaft having a length sufficient to access a patient&#39;s renal artery. A treatment element at the distal end of the shaft is dimensioned for deployment within the renal artery. The treatment element comprises a radially expandable structure configured to maintain positioning within the renal artery. A multiplicity of electrodes are spaced apart on the treatment element and configured for switchable activation and deactivation in a predetermined sequence to generate overlapping zones of heating directed at perivascular nerves of the renal artery. The overlapping heating zones comprise a distal zone associated with relatively high current densities at a distance from the treatment element sufficient to ablate the perivascular renal nerves and a proximal zone associated with current densities lower than those of the distal zone and insufficient to cause thermal injury to tissue of the renal artery adjacent the treatment element.

RELATED APPLICATIONS

This application claims the benefit of Provisional Patent ApplicationSer. Nos. 61/369,444 filed Jul. 30, 2010 and 61/418,665 filed Dec. 1,2010, to which priority is claimed pursuant to 35 U.S.C. §119(e) andwhich are hereby incorporated herein by reference in their entirety.

SUMMARY

Embodiments of the disclosure are generally directed to apparatuses andmethods for ablating target tissue of the body. Embodiments of thedisclosure are directed to apparatuses and methods for ablatinginnervated renal vasculature, such as the renal artery and renalganglia.

According to various embodiments, an apparatus includes a cathetercomprising a flexible shaft having a proximal end and a distal end. Atreatment element is provided at the distal end of the shaft. Apositioning arrangement is provided at the distal end of the shaft andconfigured to maintain positioning of the treatment element relative totarget tissue at a treatment site during ablation.

A multiplicity of electrodes defining an electrode set are arrangedrelative to one another at the treatment element. The set of electrodesis configured for switchable activation and deactivation in apredetermined sequence to generate overlapping zones of heating directedat the target tissue.

In some embodiments, the zones of heating overlap to define a distalzone associated with relatively high current densities at a distancefrom the treatment element sufficient to ablate the target tissue and aproximal zone associated with current densities lower than those of thedistal zone that cause no or negligible thermal injury to tissue at thetreatment site adjacent the treatment element.

In other embodiments, at least some of the plurality of heating zoneshave spatially separated origins at the treatment element based onactivation and deactivation of the set of electrodes. Each of theheating zones comprises a distal zone of substantially continuous ohmicheating at a distance from the treatment element sufficient to ablatethe target tissue. Each of the heating zones further comprises aproximal zone of intermittent ohmic heating proximate the treatmentelement that causes no or negligible thermal injury to tissue at thetreatment site adjacent the treatment element.

In accordance with various embodiments, an apparatus includes a cathetercomprising a flexible shaft having a proximal end, a distal end, and alength sufficient to access a patient's renal artery relative to apercutaneous location. A treatment element is provided at the distal endof the shaft and dimensioned for deployment within the renal artery. Thetreatment element comprises an expandable structure configured tomaintain positioning of the treatment element within the renal artery.

A multiplicity of electrodes defining an electrode set are arrangedrelative to one another at the treatment element. The set of electrodesis configured for switchable activation and deactivation in apredetermined sequence to generate overlapping zones of heating directedat perivascular nerves of the renal artery. The zones of heating overlapto define a distal zone associated with relatively high currentdensities at a distance from the treatment element sufficient to ablatethe perivascular renal nerves and a proximal zone associated withcurrent densities lower than those of the distal zone that cause no orinsignificant thermal injury to tissue of the renal artery adjacent thetreatment element.

An electrical conductor arrangement extends along the shaft of thecatheter and is coupled to the set of electrodes. A temperature sensorarrangement is provided at the treatment element and coupled to theelectrical conductor arrangement. The temperature sensor arrangement isconfigured to sense a temperature of the set of electrodes.

According to further embodiments, methods can be implemented formaintaining a position of a treatment element relative to target tissueat a treatment site of the body during ablation. The treatment elementpreferably includes a multiplicity of electrodes defining an electrodeset and arranged relative to one another at the treatment element. Themethods also involve switchably activating and deactivating theelectrodes in a predetermined sequence to generate overlapping zones ofheating directed at the target tissue.

In some embodiments, the zones of heating overlap to define a distalzone associated with relatively high current densities at a distancefrom the treatment element sufficient to ablate the target tissue and aproximal zone associated with current densities lower than those of thedistal zone that cause no or negligible thermal injury to tissue at thetreatment site adjacent the treatment element.

In other embodiments, at least some of the heating zones have spatiallyseparated origins at the treatment element based on activation anddeactivation of the set of electrodes. Each of the heating zonescomprises a distal zone of substantially continuous ohmic heating at adistance from the treatment element and sufficient to ablate the targettissue, and a proximal zone of intermittent ohmic heating proximate thetreatment element that causes no or negligible thermal injury to tissueat the treatment site adjacent the treatment element.

These and other features can be understood in view of the followingdetailed discussion and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a right kidney and renal vasculatureincluding a renal artery branching laterally from the abdominal aorta;

FIGS. 2A and 2B illustrate sympathetic innervation of the renal artery;

FIG. 3A illustrates various tissue layers of the wall of the renalartery;

FIGS. 3B and 3C illustrate a portion of a renal nerve;

FIG. 4A illustrates a catheter comprising a treatment element whichsupports a multiplicity of RF electrodes arranged in one or moreelectrode sets in accordance with various embodiments;

FIG. 4B is a cross section of a shaft of the catheter shown in FIG. 4Ain accordance with various embodiments;

FIG. 5 schematically illustrates overlapping areas of heating from eachseparate RF electrode of an electrode set situated on a treatmentelement of a catheter, the overlapping heating areas including a zone ofgreatest heating for nerve ablation and a cooler zone at the artery wallin accordance with various embodiments;

FIG. 6 shows a representative set of electrodes of an electrode setsituated in a spaced-apart relationship on a portion of an expandablestructure of a catheter in accordance with various embodiments;

FIG. 7 is a block diagram showing a multiplicity of electrodes andtemperature sensors situated on a portion of an expandable structure,and various components of an external control system in accordance withvarious embodiments; and

FIG. 8 shows a representative RF renal therapy apparatus in accordancewith various embodiments of the disclosure.

DESCRIPTION

In general, when using RF electrode(s) placed in the renal artery forablation of perivascular renal nerves for treatment of hypertension, thehighest current density and thus the greatest heating is typicallyadjacent to the electrode typically situated within the lumen of therenal artery. In order to achieve tissue temperatures for effectiveablation of the renal nerves, the renal artery is also injured. Activecooling can be provided but requires a larger catheter and a morecomplex system.

Embodiments of the disclosure are directed to improved RF ablationcatheters, systems, and methods. Apparatuses disclosed herein aredirected to an improved ablation catheter and system that useselectrical current. Embodiments of the disclosure are directed toapparatuses and methods for ablating perivascular renal nerves for thetreatment of hypertension.

Hypertension is a chronic medical condition in which the blood pressureis elevated. Persistent hypertension is a significant risk factorassociated with a variety of adverse medical conditions, including heartattacks, heart failure, arterial aneurysms, and strokes. Persistenthypertension is a leading cause of chronic renal failure. Hyperactivityof the sympathetic nervous system serving the kidneys is associated withhypertension and its progression. Deactivation of nerves in the kidneysvia renal denervation can reduce blood pressure, and may be a viabletreatment option for many patients with hypertension who do not respondto conventional drugs.

The kidneys are instrumental in a number of body processes, includingblood filtration, regulation of fluid balance, blood pressure control,electrolyte balance, and hormone production. One primary function of thekidneys is to remove toxins, mineral salts, and water from the blood toform urine. The kidneys receive about 20-25% of cardiac output throughthe renal arteries that branch left and right from the abdominal aorta,entering each kidney at the concave surface of the kidneys, the renalhilum.

Blood flows into the kidneys through the renal artery and the afferentarteriole, entering the filtration portion of the kidney, the renalcorpuscle. The renal corpuscle is composed of the glomerulus, a thicketof capillaries, surrounded by a fluid-filled, cup-like sac calledBowman's capsule. Solutes in the blood are filtered through the verythin capillary walls of the glomerulus due to the pressure gradient thatexists between the blood in the capillaries and the fluid in theBowman's capsule. The pressure gradient is controlled by the contractionor dilation of the arterioles. After filtration occurs, the filteredblood moves through the efferent arteriole and the peritubularcapillaries, converging in the interlobular veins, and finally exitingthe kidney through the renal vein.

Particles and fluid filtered from the blood move from the Bowman'scapsule through a number of tubules to a collecting duct. Urine isformed in the collecting duct and then exits through the ureter andbladder. The tubules are surrounded by the peritubular capillaries(containing the filtered blood). As the filtrate moves through thetubules and toward the collecting duct, nutrients, water, andelectrolytes, such as sodium and chloride, are reabsorbed into theblood.

The kidneys are innervated by the renal plexus which emanates primarilyfrom the aorticorenal ganglion. Renal ganglia are formed by the nervesof the renal plexus as the nerves follow along the course of the renalartery and into the kidney. The renal nerves are part of the autonomicnervous system which includes sympathetic and parasympatheticcomponents. The sympathetic nervous system is known to be the systemthat provides the bodies “fight or flight” response, whereas theparasympathetic nervous system provides the “rest and digest” response.Stimulation of sympathetic nerve activity triggers the sympatheticresponse which causes the kidneys to increase production of hormonesthat increase vasoconstriction and fluid retention. This process isreferred to as the renin-angiotensin-aldosterone-system (RAAS) responseto increased renal sympathetic nerve activity.

In response to a reduction in blood volume, the kidneys secrete renin,which stimulates the production of angiotensin. Angiotensin causes bloodvessels to constrict, resulting in increased blood pressure, and alsostimulates the secretion of the hormone aldosterone from the adrenalcortex. Aldosterone causes the tubules of the kidneys to increase thereabsorption of sodium and water, which increases the volume of fluid inthe body and blood pressure.

Congestive heart failure (CHF) is a condition that has been linked tokidney function. CHF occurs when the heart is unable to pump bloodeffectively throughout the body. When blood flow drops, renal functiondegrades because of insufficient perfusion of the blood within the renalcorpuscles. The decreased blood flow to the kidneys triggers an increasein sympathetic nervous system activity (i.e., the RAAS becomes tooactive) that causes the kidneys to secrete hormones that increase fluidretention and vasorestriction. Fluid retention and vasorestriction inturn increases the peripheral resistance of the circulatory system,placing an even greater load on the heart, which diminishes blood flowfurther. If the deterioration in cardiac and renal functioningcontinues, eventually the body becomes overwhelmed, and an episode ofheart failure decompensation occurs, often leading to hospitalization ofthe patient.

FIG. 1 is an illustration of a right kidney 10 and renal vasculatureincluding a renal artery 12 branching laterally from the abdominal aorta20. In FIG. 1, only the right kidney 10 is shown for purposes ofsimplicity of explanation, but reference will be made herein to bothright and left kidneys and associated renal vasculature and nervoussystem structures, all of which are contemplated within the context ofembodiments of the disclosure. The renal artery 12 is purposefully shownto be disproportionately larger than the right kidney 10 and abdominalaorta 20 in order to facilitate discussion of various features andembodiments of the present disclosure.

The right and left kidneys are supplied with blood from the right andleft renal arteries that branch from respective right and left lateralsurfaces of the abdominal aorta 20. Each of the right and left renalarteries is directed across the crus of the diaphragm, so as to formnearly a right angle with the abdominal aorta 20. The right and leftrenal arteries extend generally from the abdominal aorta 20 torespective renal sinuses proximate the hilum 17 of the kidneys, andbranch into segmental arteries and then interlobular arteries within thekidney 10. The interlobular arteries radiate outward, penetrating therenal capsule and extending through the renal columns between the renalpyramids. Typically, the kidneys receive about 20% of total cardiacoutput which, for normal persons, represents about 1200 mL of blood flowthrough the kidneys per minute.

The primary function of the kidneys is to maintain water and electrolytebalance for the body by controlling the production and concentration ofurine. In producing urine, the kidneys excrete wastes such as urea andammonium. The kidneys also control reabsorption of glucose and aminoacids, and are important in the production of hormones including vitaminD, renin and erythropoietin.

An important secondary function of the kidneys is to control metabolichomeostasis of the body. Controlling hemostatic functions includeregulating electrolytes, acid-base balance, and blood pressure. Forexample, the kidneys are responsible for regulating blood volume andpressure by adjusting volume of water lost in the urine and releasingerythropoietin and renin, for example. The kidneys also regulate plasmaion concentrations (e.g., sodium, potassium, chloride ions, and calciumion levels) by controlling the quantities lost in the urine and thesynthesis of calcitrol. Other hemostatic functions controlled by thekidneys include stabilizing blood pH by controlling loss of hydrogen andbicarbonate ions in the urine, conserving valuable nutrients bypreventing their excretion, and assisting the liver with detoxification.

Also shown in FIG. 1 is the right suprarenal gland 11, commonly referredto as the right adrenal gland. The suprarenal gland 11 is a star-shapedendocrine gland that rests on top of the kidney 10. The primary functionof the suprarenal glands (left and right) is to regulate the stressresponse of the body through the synthesis of corticosteroids andcatecholamines, including cortisol and adrenaline (epinephrine),respectively. Encompassing the kidneys 10, suprarenal glands 11, renalvessels 12, and adjacent perirenal fat is the renal fascia, e.g.,Gerota's fascia, (not shown), which is a fascial pouch derived fromextraperitoneal connective tissue.

The autonomic nervous system of the body controls involuntary actions ofthe smooth muscles in blood vessels, the digestive system, heart, andglands. The autonomic nervous system is divided into the sympatheticnervous system and the parasympathetic nervous system. In general terms,the parasympathetic nervous system prepares the body for rest bylowering heart rate, lowering blood pressure, and stimulating digestion.The sympathetic nervous system effectuates the body's fight-or-flightresponse by increasing heart rate, increasing blood pressure, andincreasing metabolism.

In the autonomic nervous system, fibers originating from the centralnervous system and extending to the various ganglia are referred to aspreganglionic fibers, while those extending from the ganglia to theeffector organ are referred to as postganglionic fibers. Activation ofthe sympathetic nervous system is effected through the release ofadrenaline (epinephrine) and to a lesser extent norepinephrine from thesuprarenal glands 11. This release of adrenaline is triggered by theneurotransmitter acetylcholine released from preganglionic sympatheticnerves.

The kidneys and ureters (not shown) are innervated by the renal nerves14. FIGS. 1 and 2A-2B illustrate sympathetic innervation of the renalvasculature, primarily innervation of the renal artery 12. The primaryfunctions of sympathetic innervation of the renal vasculature includeregulation of renal blood flow and pressure, stimulation of reninrelease, and direct stimulation of water and sodium ion reabsorption.

Most of the nerves innervating the renal vasculature are sympatheticpostganglionic fibers arising from the superior mesenteric ganglion 26.The renal nerves 14 extend generally axially along the renal arteries12, enter the kidneys 10 at the hilum 17, follow the branches of therenal arteries 12 within the kidney 10, and extend to individualnephrons. Other renal ganglia, such as the renal ganglia 24, superiormesenteric ganglion 26, the left and right aorticorenal ganglia 22, andceliac ganglia 28 also innervate the renal vasculature. The celiacganglion 28 is joined by the greater thoracic splanchnic nerve (greaterTSN). The aorticorenal ganglia 26 is joined by the lesser thoracicsplanchnic nerve (lesser TSN) and innervates the greater part of therenal plexus.

Sympathetic signals to the kidney 10 are communicated via innervatedrenal vasculature that originates primarily at spinal segments T10-T12and L1. Parasympathetic signals originate primarily at spinal segmentsS2-S4 and from the medulla oblongata of the lower brain. Sympatheticnerve traffic travels through the sympathetic trunk ganglia, where somemay synapse, while others synapse at the aorticorenal ganglion 22 (viathe lesser thoracic splanchnic nerve, i.e., lesser TSN) and the renalganglion 24 (via the least thoracic splanchnic nerve, i.e., least TSN).The postsynaptic sympathetic signals then travel along nerves 14 of therenal artery 12 to the kidney 10. Presynaptic parasympathetic signalstravel to sites near the kidney 10 before they synapse on or near thekidney 10.

With particular reference to FIG. 2A, the renal artery 12, as with mostarteries and arterioles, is lined with smooth muscle 34 that controlsthe diameter of the renal artery lumen 13. Smooth muscle, in general, isan involuntary non-striated muscle found within the media layer of largeand small arteries and veins, as well as various organs. The glomeruliof the kidneys, for example, contain a smooth muscle-like cell calledthe mesangial cell. Smooth muscle is fundamentally different fromskeletal muscle and cardiac muscle in terms of structure, function,excitation-contraction coupling, and mechanism of contraction.

Smooth muscle cells can be stimulated to contract or relax by theautonomic nervous system, but can also react on stimuli from neighboringcells and in response to hormones and blood borne electrolytes andagents (e.g., vasodilators or vasoconstrictors). Specialized smoothmuscle cells within the afferent arteriole of the juxtaglomerularapparatus of kidney 10, for example, produces renin which activates theangiotension II system.

The renal nerves 14 innervate the smooth muscle 34 of the renal arterywall 15 and extend lengthwise in a generally axial or longitudinalmanner along the renal artery wall 15. The smooth muscle 34 surroundsthe renal artery circumferentially, and extends lengthwise in adirection generally transverse to the longitudinal orientation of therenal nerves 14, as is depicted in FIG. 2B.

The smooth muscle 34 of the renal artery 12 is under involuntary controlof the autonomic nervous system. An increase in sympathetic activity,for example, tends to contract the smooth muscle 34, which reduces thediameter of the renal artery lumen 13 and decreases blood perfusion. Adecrease in sympathetic activity tends to cause the smooth muscle 34 torelax, resulting in vessel dilation and an increase in the renal arterylumen diameter and blood perfusion. Conversely, increasedparasympathetic activity tends to relax the smooth muscle 34, whiledecreased parasympathetic activity tends to cause smooth musclecontraction.

FIG. 3A shows a segment of a longitudinal cross-section through a renalartery, and illustrates various tissue layers of the wall 15 of therenal artery 12. The innermost layer of the renal artery 12 is theendothelium 30, which is the innermost layer of the intima 32 and issupported by an internal elastic membrane. The endothelium 30 is asingle layer of cells that contacts the blood flowing though the vessellumen 13. Endothelium cells are typically polygonal, oval, or fusiform,and have very distinct round or oval nuclei. Cells of the endothelium 30are involved in several vascular functions, including control of bloodpressure by way of vasoconstriction and vasodilation, blood clotting,and acting as a barrier layer between contents within the lumen 13 andsurrounding tissue, such as the membrane of the intima 32 separating theintima 32 from the media 34, and the adventitia 36. The membrane ormaceration of the intima 32 is a fine, transparent, colorless structurewhich is highly elastic, and commonly has a longitudinal corrugatedpattern.

Adjacent the intima 32 is the media 33, which is the middle layer of therenal artery 12. The media is made up of smooth muscle 34 and elastictissue. The media 33 can be readily identified by its color and by thetransverse arrangement of its fibers. More particularly, the media 33consists principally of bundles of smooth muscle fibers 34 arranged in athin plate-like manner or lamellae and disposed circularly around thearterial wall 15. The outermost layer of the renal artery wall 15 is theadventitia 36, which is made up of connective tissue. The adventitia 36includes fibroblast cells 38 that play an important role in woundhealing.

A perivascular region 37 is shown adjacent and peripheral to theadventitia 36 of the renal artery wall 15. A renal nerve 14 is shownproximate the adventitia 36 and passing through a portion of theperivascular region 37. The renal nerve 14 is shown extendingsubstantially longitudinally along the outer wall 15 of the renal artery12. The main trunk of the renal nerves 14 generally lies in or on theadventitia 36 of the renal artery 12, often passing through theperivascular region 37, with certain branches coursing into the media 33to enervate the renal artery smooth muscle 34.

Embodiments of the disclosure may be implemented to provide varyingdegrees of denervation therapy to innervated renal vasculature. Forexample, embodiments of the disclosure may provide for control of theextent and relative permanency of renal nerve impulse transmissioninterruption achieved by denervation therapy delivered using a treatmentapparatus of the disclosure. The extent and relative permanency of renalnerve injury may be tailored to achieve a desired reduction insympathetic nerve activity (including a partial or complete block) andto achieve a desired degree of permanency (including temporary orirreversible injury).

Returning to FIGS. 3B and 3C, the portion of the renal nerve 14 shown inFIGS. 3B and 3C includes bundles 14 a of nerve fibers 14 b eachcomprising axons or dendrites that originate or terminate on cell bodiesor neurons located in ganglia or on the spinal cord, or in the brain.Supporting tissue structures 14 c of the nerve 14 include theendoneurium (surrounding nerve axon fibers), perineurium (surroundsfiber groups to form a fascicle), and epineurium (binds fascicles intonerves), which serve to separate and support nerve fibers 14 b andbundles 14 a. In particular, the endoneurium, also referred to as theendoneurium tube or tubule, is a layer of delicate connective tissuethat encloses the myelin sheath of a nerve fiber 14 b within afasciculus.

Major components of a neuron include the soma, which is the central partof the neuron that includes the nucleus, cellular extensions calleddendrites, and axons, which are cable-like projections that carry nervesignals. The axon terminal contains synapses, which are specializedstructures where neurotransmitter chemicals are released in order tocommunicate with target tissues. The axons of many neurons of theperipheral nervous system are sheathed in myelin, which is formed by atype of glial cell known as Schwann cells. The myelinating Schwann cellsare wrapped around the axon, leaving the axolemma relatively uncoveredat regularly spaced nodes, called nodes of Ranvier. Myelination of axonsenables an especially rapid mode of electrical impulse propagationcalled saltation.

In some embodiments, a treatment apparatus of the disclosure may beimplemented to deliver denervation therapy that causes transient andreversible injury to renal nerve fibers 14 b. In other embodiments, atreatment apparatus of the disclosure may be implemented to deliverdenervation therapy that causes more severe injury to renal nerve fibers14 b, which may be reversible if the therapy is terminated in a timelymanner. In preferred embodiments, a treatment apparatus of thedisclosure may be implemented to deliver denervation therapy that causessevere and irreversible injury to renal nerve fibers 14 b, resulting inpermanent cessation of renal sympathetic nerve activity. For example, atreatment apparatus may be implemented to deliver a denervation therapythat disrupts nerve fiber morphology to a degree sufficient tophysically separate the endoneurium tube of the nerve fiber 14 b, whichcan prevent regeneration and re-innervation processes.

By way of example, and in accordance with Seddon's classification as isknown in the art, a treatment apparatus of the disclosure may beimplemented to deliver a denervation therapy that interrupts conductionof nerve impulses along the renal nerve fibers 14 b by imparting damageto the renal nerve fibers 14 b consistent with neruapraxia. Neurapraxiadescribes nerve damage in which there is no disruption of the nervefiber 14 b or its sheath. In this case, there is an interruption inconduction of the nerve impulse down the nerve fiber, with recoverytaking place within hours to months without true regeneration, asWallerian degeneration does not occur. Wallerian degeneration refers toa process in which the part of the axon separated from the neuron's cellnucleus degenerates. This process is also known as anterogradedegeneration. Neurapraxia is the mildest form of nerve injury that maybe imparted to renal nerve fibers 14 b by use of a treatment apparatusaccording to embodiments of the disclosure.

A treatment apparatus may be implemented to interrupt conduction ofnerve impulses along the renal nerve fibers 14 b by imparting damage tothe renal nerve fibers consistent with axonotmesis. Axonotmesis involvesloss of the relative continuity of the axon of a nerve fiber and itscovering of myelin, but preservation of the connective tissue frameworkof the nerve fiber. In this case, the encapsulating support tissue 14 cof the nerve fiber 14 b are preserved. Because axonal continuity islost, Wallerian degeneration occurs. Recovery from axonotmesis occursonly through regeneration of the axons, a process requiring time on theorder of several weeks or months. Electrically, the nerve fiber 14 bshows rapid and complete degeneration. Regeneration and re-innervationmay occur as long as the endoneural tubes are intact.

A treatment apparatus may be implemented to interrupt conduction ofnerve impulses along the renal nerve fibers 14 b by imparting damage tothe renal nerve fibers 14 b consistent with neurotmesis. Neurotmesis,according to Seddon's classification, is the most serious nerve injuryin the scheme. In this type of injury, both the nerve fiber 14 b and thenerve sheath are disrupted. While partial recovery may occur, completerecovery is not possible. Neurotmesis involves loss of continuity of theaxon and the encapsulating connective tissue 14 c, resulting in acomplete loss of autonomic function, in the case of renal nerve fibers14 b. If the nerve fiber 14 b has been completely divided, axonalregeneration causes a neuroma to form in the proximal stump.

A more stratified classification of neurotmesis nerve damage may befound by reference to the Sunderland System as is known in the art. TheSunderland System defines five degrees of nerve damage, the first two ofwhich correspond closely with neurapraxia and axonotmesis of Seddon'sclassification. The latter three Sunderland System classificationsdescribe different levels of neurotmesis nerve damage.

The first and second degrees of nerve injury in the Sunderland systemare analogous to Seddon's neurapraxia and axonotmesis, respectively.Third degree nerve injury, according to the Sunderland System, involvesdisruption of the endoneurium, with the epineurium and perineuriumremaining intact. Recovery may range from poor to complete depending onthe degree of intrafascicular fibrosis. A fourth degree nerve injuryinvolves interruption of all neural and supporting elements, with theepineurium remaining intact. The nerve is usually enlarged. Fifth degreenerve injury involves complete transection of the nerve fiber 14 b withloss of continuity.

Embodiments of the disclosure are directed to apparatuses and methodsthat provide an improved way of reducing injury to the renal arteryduring ablation of the renal nerves. Various embodiments are directed toapparatuses and methods for reducing injury to other tissues andstructures of the body when ablating nearby target tissue. Examples ofsuch other body tissues, structures, and target tissue include organs,tumors, diseased tissue, and vasculature of the heart, such as pulmonaryveins or electrically active target cardiac tissue for treatment ofcardiac rhythm pathologies.

Embodiments of the disclosure are directed to apparatuses and methodsfor ablation of perivascular renal nerves for treatment of hypertension,using electrical current. As previously discussed, when using an RFelectrode placed in the renal artery, the highest current density andthus the area of greatest heating and injury is typically adjacent tothe electrode. Embodiments of the disclosure provide for sufficientablation of target nerves while reducing injury to the renal artery bymoving the current among a set of nearby RF electrodes.

According to various embodiments, when one electrode is activated, theartery wall section adjacent to the other electrodes can cool. Thecurrent is switched to a different electrode in the set, allowing theartery wall section adjacent to the first electrode to cool. The currentspreads out somewhat in the perivascular tissue, so that the regionsheated by activating each electrode in the set overlap, preventingcooling of the target tissue.

Referring now to FIG. 4A, there is illustrated a catheter 100 whichincludes a multiplicity of sequentially activatable RF electrodes forablating target tissue of a treatment site. FIG. 4A is a simplifiedschematic representation provided for purposes of explanation. It isunderstood that an inner lumen through the balloon 102 can be used forguidewire passage while maintaining balloon inflation, and that theguidewire hole 111 is a schematic representation of the distal end ofthis inner lumen.

According to some embodiments, the catheter 100 includes a flexibleshaft 104 having a proximal end and a distal end. A treatment element101 is provided at the distal end of the shaft 104. A positioningarrangement 102 is provided at the distal end of the shaft 204 andconfigured to maintain positioning of the treatment element 101 relativeto target tissue at a treatment site during ablation. The positioningarrangement 102 preferably includes a radially expandable structure 103,such as a balloon or a mesh structure. In the embodiment shown in FIG.4A, the treatment arrangement 101 and the positioning arrangement 102are collocated on a common structure (e.g., expandable structure 103).In other embodiments, the treatment arrangement 101 and the positioningarrangement 102 can be situated on separate structures of the catheter100.

According to some embodiments, the shaft 104 of the catheter 100 has alength sufficient to access a patient's renal artery 12 relative to apercutaneous location. The treatment element 101 provided at the distalend of the shaft 204 is dimensioned for deployment within the renalartery 12. The treatment element 101 comprises a radially expandablestructure 103 configured to maintain positioning of the treatmentelement 101 within the renal artery 12, such as a balloon or meshstructure.

FIG. 4B shows a cross section of the shaft 104 of the catheter 100 ofFIG. 4A, which includes an electrode conductor lumen 113 a, a sensorconductor lumen 113 b, a guide wire lumen 111, a supply lumen 106, and areturn lumen 108. The supply and return lumens 106, 108 respectivelydeliver and remove a pressurizing fluid to and from the balloon 102during inflation and deflation operations.

The electrode and sensor conductor lumens 113 a, 113 b may each includea layer of electrically insulating material and/or the conductorsdisposed therein may each include an insulating layer. In variousembodiments, each of the electrodes 120 of a given electrode set 119 isconnected to an electrical conductor arrangement 110 of the catheter 100via individual electrical conductors that extend through the electrodeconductor lumen 113 a.

A temperature sensor arrangement 121 is shown in FIG. 4A and includes amultiplicity of temperature sensors 123 distributed within the electrodeset 119. The temperature sensor arrangement 121 is configured to sense atemperature at or proximate the set 119 of electrodes 120. Each of thetemperature sensors 123 of a given temperature sensor arrangement 121 isconnected to the electrical conductor arrangement 110 of the catheter100 via individual electrical conductors that extend through the sensorconductor lumen 113 b. The electrical conductor arrangement 110 extendsalong the shaft 104 to a proximal end of the catheter 100.

It is noted that each electrode 120 need not have an associatedtemperature sensor 123, and that one, two or a few (i.e., a number lessthan the number of electrodes 120) temperature sensors 123 may bedeployed for an electrode set 119. In some embodiments, for example,temperatures sensing is not used, in view of the local cooling at theelectrode-tissue interface provided by the time activation and spatiallocation arrangements of the set 119 of electrodes 120.

The guide wire lumen 111 is dimensioned to receive a guide wire or otherelongated navigation assist member that can by used by the clinician tofacilitate delivery of the balloon 102 into a desired treatmentlocation, such as a renal artery. In the configuration shown in FIG. 4A,the guide wire lumen 111 defines an open lumen of the balloon 102, whichallows for advancement of a guide wire therethrough for navigating theballoon 102 to the renal artery, for example. After the guide wire ispositioned within the renal artery, the balloon catheter 100 is advancedalong the guide wire and delivered to the lumen of the renal arteryusing an over-the-wire delivery technique.

As is shown in FIGS. 4A and 5, a multiplicity of electrodes 120 definean electrode set 119 and are arranged relative to one another at thetreatment element 101. The electrodes 120 of the electrode set 119 areconfigured for switchable activation and deactivation in a predeterminedsequence to generate overlapping zones of heating 240 directed at thetarget tissue. For example, individual electrodes within an electrodeset can be energized in a predetermined sequence, or multiple electrodeswithin a set can be energized simultaneously, such as electrodes 1 and3, followed by 2 and 4, and so forth. Energizing of electrodes canpartially overlap in time. Specific electrodes can be energized usingdifferent electrical waveforms to enhance target tissue heating whilereducing artery wall injury. FIG. 5 schematically illustratesoverlapping areas of heating from each separate RF electrode 120, and azone of greatest heating for nerve ablation, and a cooler zone at theartery wall.

It is noted that in FIG. 5, shaded cones are used to schematicallyrepresent zones of higher current density. It is understood that actualfield and current lines are more complicated and are dependent on anumber of factors, including impedance of the various tissues and thelocation of the return electrode(s) (e.g., an external skin pad or asecond electrode if a bipolar arrangement is used).

FIG. 5 illustrates an area of less overlapping current paths on theartery wall which would be cooler due to intermittent heating, and anarea of more continuous current and greater heating in the target tissuea short distance away. For example, The zones of heating 240 in FIG. 5overlap to define a distal zone 250, associated with relatively highcurrent densities at a distance from the treatment element 101sufficient to ablate the target tissue, and a proximal zone 260,associated with current densities lower than those of the distal zonethat cause no or negligible thermal injury to tissue at the treatmentsite adjacent the treatment element 101.

The current densities associated with the proximal zone of heating 260are preferably lower than a current density required to causecoagulative necrosis of tissue at the treatment site adjacent thetreatment element 101. For example, the current densities associatedwith the proximal zone of heating 260 are preferably insufficient tocause heating of tissue adjacent the treatment element 101 to atemperature above about 50° C. The current densities associated with thedistal zone of heating 250, in contrast, are preferably sufficient tocause heating of the target tissue to a temperature of at least about55° C.

In accordance with various embodiments, at least some of the heatingzones 240 have spatially separated origins at the treatment element 101based on selective activation and deactivation of the set 119 ofelectrodes 120. Each of the heating zones 240 comprises a distal zone250 of substantially continuous ohmic heating at a distance from thetreatment element 101 and sufficient to ablate the target tissue. Eachof the heating zones 240 also comprises a proximal zone 260 ofintermittent ohmic heating proximate the treatment element 101 thatcauses no or insubstantial thermal injury to tissue at the treatmentsite adjacent the treatment element 101.

According to some embodiments, the electrodes 120 of the electrode set119 are configured for switchable activation and deactivation in apredetermined sequence to generate overlapping zones of heating 240directed at perivascular nerves of the renal artery 12. The zones ofheating 240 overlap to define a distal zone 250 associated withrelatively high current densities at a distance from the treatmentelement 101 sufficient to ablate the perivascular renal nerves, and aproximal zone 260 associated with current densities lower than those ofthe distal zone 250 that cause no or insubstantial thermal injury totissue of the renal artery 12 adjacent the treatment element 101.

In various embodiments, the time activation arrangement and spatiallocation arrangement of the set 119 of electrodes 120 can be selected tospare substantial portions of the renal artery wall, even if renalartery tissue located immediately adjacent the electrodes 120 is subjectto thermal injury. Accordingly, only an insignificant percentage ofrenal artery tissue (i.e., that small percentage of renal artery tissuelocated immediately adjacent the electrodes 120) is subject to possiblethermally injury during ablation.

In some embodiments, it may be desirable to include a coolingarrangement that enhances local cooling at the electrode-tissueinterface in addition to the cooling provided by the time activation andspatial location arrangements of the set 119 of electrodes 120. Bloodperfusion lumens can be incorporated in or on the treatment element 101and used to provide cooling for the wall of the renal artery 12 duringablation of the perivascular renal nerves. For example, a cooling lumenarrangement can be configured to shunt blood passing through the renalartery 12 to cool the electrodes supported by the treatment element 101during ablation.

In some embodiments, the cooling arrangement may constitute longitudinalor spiral channels or flutes built into the treatment element 101. Bloodpassing through channels or flutes serves to enhance cooling of the wallof the renal artery 12 during ablation. Passive or active coolingmechanisms can synergistically enhance the artery wall protectionoffered by embodiments of the disclosure.

According to some approaches, experiments can be performed to determinewhich combinations of activation sequence and power settings proveefficacious, from which a standard activation regimen can be establishedand used. A simple temperature measurement or electrical measurement(e.g., impedance, current, or voltage sensing or a combination thereof)could be combined with a standard activation regimen for limitedcustomization or adjustment, such as using standard sequence and powerratios and timing, simply scaled in magnitude or time by using thesimple temperature or electrical measurement.

Referring now to FIG. 6, a representative set 119 of electrodes 120 areshown situated in a spaced-apart relationship on a portion of anexpandable structure 103. A temperature sensor arrangement 121 issituated on the expandable structure 103 in close proximity to the set119 of electrodes 120. As shown in FIG. 6, an individual temperaturesensor 123 of the temperature sensor arrangement 121 is situatedproximate each of the electrodes 120 of the electrode set 119.

As is shown in FIGS. 5 and 6, one or more temperature sensors 123, suchas thermocouples, are provided at the site of the electrode set 119 tomeasure the temperature of the electrode set 119. In some embodiments, atemperature sensor 123 is positioned near or at the site of eachelectrode 120 of the electrode set 123, allowing for precisiontemperature measurements at individual electrode locations of theablation electrode arrangement 101.

A set of electrical conductors 127 is arranged on the expandablestructure 103 for establishing electrical connection between eachelectrode 120 of the electrode set 119 and external electrode activationcircuitry. A set of electrical conductors 129 is arranged on theexpandable structure 103 for establishing electrical connection betweeneach temperature sensor 123 of the temperature sensor arrangement 121and external temperature sensor circuitry.

In some embodiments, the electrical conductors 127 and 129 can be formedusing a metalized layer in combination with a non-conductive polymermaterial used to construct the expandable structure 103 (e.g., balloon)and appropriate masking In other embodiments, the electrical conductors127 and 129 can be formed using a conductive wire mesh in combinationwith a non-conductive material or coating and appropriate masking. Infurther embodiments, the wire mesh structure can be a wire mesh or braidor basket. Depending on the electrical features of a particularimplementation, the wire mesh structure can comprise insulated ornon-insulated conductive wires, or non-conductive or polymericstructures, or combinations thereof.

In one configuration, a set 119 of eight unipolar electrodes 123 isaffixed to an expandable balloon or wire mesh structure 103 to maintainpositioning within the renal artery. The set of electrical conductors127 is connected to external electrode activation circuitry whichactivates each RF electrode 120 in a sequence to allow cooling of theartery 12, but maintain desired heating in the target tissue. Othernumbers of electrodes can be used, such as a set of five electrodesactivated in the sequence 1-3-5-2-4 and repeating, or other sequencechosen for maximal artery cooling.

One or more additional sets 119 of electrodes 123 located at other areason the renal artery wall can be used to ablate different portions of theperivascular renal nerves, or the catheter and/or expandable structure103 can be moved to a different location and activated again.

According various embodiments, bipolar electrode sets can be used,mixing the locations of activated electrodes 123 to maintain heating oftarget tissue but allow the artery to heat and cool intermittently tominimize artery injury. A similar approach can be used with otherheating mechanisms to generate heat in a sequence of adjacent locationsthat intersect to create a heated zone to ablate the target tissue and acooler zone to protect the artery 12. A similar approach can be used toablate target tissue a short distance away, while protecting tissuecloser to the heating device, such as for tumor ablation or BPH (benignprostatic hypertrophy) treatment.

FIG. 7 is a block diagram showing a multiplicity of electrodes andtemperature sensors situated on a portion of an expandable structure103, and various components of an external control system in accordancewith various embodiments. In some embodiments, it may be desirable touse more than one electrode set 119 disposed on an expandable structure103 of a catheter 101. Two, three, or four electrode sets 119 may besituated on the expandable structure 103 at different longitudinal andcircumferential locations. For example, four offset electrode sets 119each covering a different 90° of arc on the expandable structure 103 canbe deployed to define a generally spiral shape. By way of furtherexample, three electrode sets 119 each covering a different 120° of arcon the expandable structure 103 can be deployed to define a generallycircumferential shape.

The portion of the expandable structure 103 shown in FIG. 7 includes amultiplicity of electrode sets 119 a-119 n, each of which comprisesseveral independently controlled electrodes 120. Each of the electrodesets 119 a-119 n is electrically coupled to external electrodeactivation circuitry 320. As discussed previously, each electrode 120 ofeach electrode set 119 a-119 n is separately coupled to the externalelectrode activation circuitry 320.

The portion of the expandable structure 103 shown in FIG. 7 alsoincludes a multiplicity of temperature sensor arrays 121 a-121 n, eachof which comprises several independent temperature sensors 123. Each ofthe temperature sensor arrays 121 a-121 n is electrically coupled toexternal temperature measuring circuitry 328. Each temperature sensor123 of each temperature sensor array 121 a-121 n is separately coupledto the external temperature measuring circuitry 328.

The external temperature measuring circuitry 328 is coupled to theexternal electrode activation circuitry 320. Temperature information foreach temperature sensor 123 of each temperature sensor array 121 a-121 nis provided to the external electrode activation circuitry 320 by theexternal temperature measuring circuitry 328. The external electrodeactivation circuitry 320 includes power control 322 and timing control324. Based in part on received temperature information, the externalelectrode activation circuitry 320 controls the activation sequence of,and amount of RF energy supplied to, each electrode 123 of eachelectrode set 119 a-119 n.

FIG. 8 shows a representative RF renal therapy apparatus 300 inaccordance with various embodiments of the disclosure. The apparatus 300illustrated in FIG. 8 includes external electrode activation circuitry320 which comprises power control circuitry 322 and timing controlcircuitry 324. The external electrode activation circuitry 320, whichincludes an RF generator, is coupled to temperature measuring circuitry328 and may be coupled to an optional impedance sensor 326. The catheter100 includes a shaft 104 that incorporates a lumen arrangement 105configured for receiving a variety of components, such as conductors,inflation fluids, pharmacological agents, actuator elements, obturators,sensors, or other components as needed or desired.

The RF generator of the external electrode activation circuitry 320 mayinclude a return pad electrode 330 that is configured to comfortablyengage the patient's back or other portion of the body near the kidneys.Radiofrequency energy produced by the RF generator is coupled to thetreatment element 101 at the distal end of the catheter 101 by theconductor arrangement 110 disposed in the lumen of the catheter's shaft104.

Renal denervation therapy using the apparatus shown in FIG. 8 istypically performed using one or more electrode sets 119 of thetreatment element 101 positioned within the renal artery and the returnpad electrode 330 positioned on the patient's back, with the RFgenerator operating in a monopolar mode. In this implementation, theelectrodes 120 of the one or more electrode sets 119 are configured foroperation in a unipolar configuration. In other implementations, theelectrodes 120 of the one or more electrode sets 119 can be configuredfor operation in a bipolar configuration, in which case the returnelectrode pad 330 is not needed.

The radiofrequency energy flows through the one or more electrode sets119 in accordance with a predetermined activation sequence causingcurrent flow and Joule heating in the adjacent tissue of the renalartery. Sequential activation of the electrodes 120 serves to generateoverlapping heating zones as described hereinabove, with each heatingzone comprising a distal zone of substantially continuous ohmic heatingat a distance from the treatment element 101 sufficient to ablateperivascular renal nerves, and a proximal zone of intermittent ohmicheating proximate the treatment element 101 insufficient to causethermal injury to the renal artery tissue adjacent the treatment element101.

In general, when renal artery tissue temperatures rise above about 113°F. (50° C.), protein is permanently damaged (including those of renalnerve fibers). For example, any mammalian tissue that is heated aboveabout 50° C. for even 1 second is killed. If heated over about 65° C.,collagen denatures and tissue shrinks If heated over about 65° C. and upto 100° C., cell walls break and oil separates from water. Above about100° C., tissue desiccates.

According to some embodiments, the electrode activation circuitry 320 isconfigured to control activation and deactivation of the electrodes 120of one or more electrode sets 119 in accordance with a predeterminedsequence and in response to signals received from temperature measuringcircuitry 328. The electrode activation circuitry 320 controlsradiofrequency energy delivered to the electrodes 120 so as to maintainthe current densities within the distal zone of heating at a levelsufficient to cause heating of the target tissue to at least atemperature of 65° C. and to maintain the current densities within theproximal zone of heating to a level insufficient to cause heating oftissue adjacent the treatment element to a temperature above 50° C.

Temperature sensors 123 situated at the treatment element 101 providefor continuous monitoring of renal artery tissue temperatures, and RFgenerator power is automatically adjusted so that the targettemperatures are achieved and maintained. An impedance sensorarrangement 326 may be used to measure and monitor electrical impedanceduring RF denervation therapy, and the power and timing of the RFgenerator 320 may be moderated based on the impedance measurements or acombination of impedance and temperature measurements. The size of theablated area is determined largely by the size, number, and shape of theelectrodes 123 at the treatment element 101, the power applied, and theduration of time the energy is applied.

Marker bands 314 can be placed on one or multiple parts of the treatmentelement 101 to enable visualization during the procedure. Other portionsof the catheter 101, such as one or more portions of the shaft 104(e.g., at the hinge mechanism 356), may include a marker band 314. Themarker bands 314 may be solid or split bands of platinum or otherradiopaque metal, for example. Radiopaque materials are understood to bematerials capable of producing a relatively bright image on afluoroscopy screen or another imaging technique during a medicalprocedure. This relatively bright image aids the user in determiningspecific portions of the catheter 100, such as the tip of the catheter101, the treatment element 101, and the hinge 356, for example. A braidand/or electrodes of the catheter 100, according to some embodiments,can be radiopaque, and a balloon can be filled with contrast/saline if aballoon is used as part of the expandable structure 103.

Various embodiments disclosed herein are generally described in thecontext of ablation of perivascular renal nerves for control ofhypertension. It is understood, however, that embodiments of thedisclosure have applicability in other contexts, such as performingablation from within other vessels of the body, including otherarteries, veins, and vasculature (e.g., cardiac and urinary vasculatureand vessels), and other tissues of the body, including various organs.

It is to be understood that even though numerous characteristics ofvarious embodiments have been set forth in the foregoing description,together with details of the structure and function of variousembodiments, this detailed description is illustrative only, and changesmay be made in detail, especially in matters of structure andarrangements of parts illustrated by the various embodiments to the fullextent indicated by the broad general meaning of the terms in which theappended claims are expressed.

What is claimed is:
 1. A method, comprising: positioning a treatmentelement within a blood vessel lumen adjacent target tissue at atreatment site of a body, the treatment element comprising a pluralityof electrodes defining an electrode set and arranged relative to oneanother at the treatment element; maintaining a position of thetreatment element relative to target tissue at the treatment site of thebody during ablation; and switchably activating and deactivating theelectrodes in a predetermined sequence to generate overlapping zones ofheating directed at the target tissue; the zones of heating overlappingto define a distal zone associated with relatively high currentdensities at a distance from the treatment element sufficient to ablatethe target tissue and a proximal zone associated with current densitieslower than those of the distal zone that cause no or negligible thermalinjury to tissue at the treatment site adjacent the treatment element.2. The method of claim 1, wherein at least some of the heating zoneshave spatially separated origins at the treatment element based onactivation and deactivation of the set of electrodes, each of theheating zones comprising: a distal zone of substantially continuousohmic heating at a distance from the treatment element and sufficient toablate the target tissue; and a proximal zone of intermittent ohmicheating proximate the treatment element that causes insignificantthermal injury to tissue at the treatment site adjacent the treatmentelement.
 3. The method of claim 1, comprising providing cooling at anelectrode-tissue interface defined between the treatment element andtissue at the treatment site adjacent the treatment element.
 4. Themethod of claim 1, wherein: maintaining treatment element positioningcomprising maintaining the position of the treatment element within arenal artery during ablation; the distal zone is associated with currentdensities sufficient to ablate perivascular renal nerves; and theproximal zone is associated with current densities that cause no ornegligible thermal injury to tissue of the renal artery adjacent thetreatment element.